Aims To quantify the association of combined sleep behaviours and genetic susceptibility with the incidence of cardiovascular disease (CVD). Methods and results This study included 385 292 participants initially free of CVD from UK Biobank. We newly created a healthy sleep score according to five sleep factors and defined the low-risk groups as follows: early chronotype, sleep 7–8 h per day, never/rarely insomnia, no snoring, and no frequent excessive daytime sleepiness. Weighted genetic risk scores of coronary heart disease (CHD) or stroke were calculated. During a median of 8.5 years of follow-up, we documented 7280 incident CVD cases including 4667 CHD and 2650 stroke cases. Compared to those with a sleep score of 0–1, participants with a score of 5 had a 35% (19–48%), 34% (22–44%), and 34% (25–42%) reduced risk of CVD, CHD, and stroke, respectively. Nearly 10% of cardiovascular events in this cohort could be attributed to poor sleep pattern. Participants with poor sleep pattern and high genetic risk showed the highest risk of CHD and stroke. Conclusion In this large prospective study, a healthy sleep pattern was associated with reduced risks of CVD, CHD, and stroke among participants with low, intermediate, or high genetic risk.

SUMMARY Meta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D) 1 , 2 , however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1 , PTF1A , SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation 3 . At another locus, eQTLs at two overlapping T2D signals affect two genes, NKX6-3 and ANK1 , in different tissues 4 – 6 . Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.

Background-Genetic variation plays an important role in the development of non-small cell lung cancer (NSCLC). However, major genetic factors for lung cancer have not been fully identified, especially in Chinese populations, which deters us from using a polygenic risk score (PRS) to identify sub-populations at high-risk of lung cancer for prevention.Methods-To systematically identify genetic variants for NSCLC risk, we newly genotyped 19,546 samples and conducted a meta-analysis of genome-wide association studies (GWASs) of Dai et al.

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Stroke is the second leading cause of death worldwide accounting for >6M deaths annually (including 2M stroke deaths in China)1,2. Both ischaemic stroke (IS) and haemorrhagic stroke (chiefly intracerebral haemorrhage [ICH]), account for an equal number of stroke deaths in China, despite the incidence of IS being about 4-fold greater than ICH1,2. China also has a higher incidence of stroke and a higher proportion of ICH, compared with Western populations3–5, despite having a lower mean low-density lipoprotein cholesterol (LDL-C) concentration. Observational studies reported weaker positive associations of LDL-C with IS than with coronary heart disease (CHD)6,7, but LDL-C-lowering trials demonstrated similar risk reductions for IS and CHD8–10. Mendelian randomisation (MR) studies of LDL-C and IS have reported conflicting results11–13, prompting questions about the importance of LDL-C for IS. Concerns about the excess risks of ICH associated with lowering LDL-C14,15, may have prevented the more widespread use of statins for prevention of cardiovascular disease (CVD) in China. We examined the associations of biochemically-measured LDL-C, and of other major lipids, with IS and ICH in a nested case-control study in the China Kadoorie Biobank (CKB), and compared the risks for both stroke types associated with equivalent differences in LDL-C in MR analyses, and with worldwide LDL-C-lowering trials. The results demonstrated strong positive associations of LDL-C with IS and equally strong inverse associations with ICH, that were confirmed by genetic analyses and by LDL-C-lowering trials, but lowering LDL-C is still likely to have net benefit for prevention of overall stroke and CVD in China.